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Unexpected steric hindrance failure in the gas phase F(−) + (CH(3))(3)CI S(N)2 reaction

Base-induced elimination (E2) and bimolecular nucleophilic substitution (S(N)2) reactions are of significant importance in physical organic chemistry. The textbook example of the retardation of S(N)2 reactivity by bulky alkyl substitution is widely accepted based on the static analysis of molecular...

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Autores principales: Lu, Xiaoxiao, Shang, Chenyao, Li, Lulu, Chen, Rongjun, Fu, Bina, Xu, Xin, Zhang, Dong H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338938/
https://www.ncbi.nlm.nih.gov/pubmed/35907925
http://dx.doi.org/10.1038/s41467-022-32191-6
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author Lu, Xiaoxiao
Shang, Chenyao
Li, Lulu
Chen, Rongjun
Fu, Bina
Xu, Xin
Zhang, Dong H.
author_facet Lu, Xiaoxiao
Shang, Chenyao
Li, Lulu
Chen, Rongjun
Fu, Bina
Xu, Xin
Zhang, Dong H.
author_sort Lu, Xiaoxiao
collection PubMed
description Base-induced elimination (E2) and bimolecular nucleophilic substitution (S(N)2) reactions are of significant importance in physical organic chemistry. The textbook example of the retardation of S(N)2 reactivity by bulky alkyl substitution is widely accepted based on the static analysis of molecular structure and steric environment. However, the direct dynamical evidence of the steric hindrance of S(N)2 from experiment or theory remains rare. Here, we report an unprecedented full-dimensional (39-dimensional) machine learning-based potential energy surface for the 15-atom F(−) + (CH(3))(3)CI reaction, facilitating the reliable and efficient reaction dynamics simulations that can reproduce well the experimental outcomes and examine associated atomic-molecular level mechanisms. Moreover, we found surprisingly high “intrinsic” reactivity of S(N)2 when the E2 pathway is completely blocked, indicating the reaction that intends to proceed via E2 transits to S(N)2 instead, due to a shared pre-reaction minimum. This finding indicates that the competing factor of E2 but not the steric hindrance determines the small reactivity of S(N)2 for the F(−) + (CH(3))(3)CI reaction. Our study provides new insight into the dynamical origin that determines the intrinsic reactivity in gas-phase organic chemistry.
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spelling pubmed-93389382022-08-01 Unexpected steric hindrance failure in the gas phase F(−) + (CH(3))(3)CI S(N)2 reaction Lu, Xiaoxiao Shang, Chenyao Li, Lulu Chen, Rongjun Fu, Bina Xu, Xin Zhang, Dong H. Nat Commun Article Base-induced elimination (E2) and bimolecular nucleophilic substitution (S(N)2) reactions are of significant importance in physical organic chemistry. The textbook example of the retardation of S(N)2 reactivity by bulky alkyl substitution is widely accepted based on the static analysis of molecular structure and steric environment. However, the direct dynamical evidence of the steric hindrance of S(N)2 from experiment or theory remains rare. Here, we report an unprecedented full-dimensional (39-dimensional) machine learning-based potential energy surface for the 15-atom F(−) + (CH(3))(3)CI reaction, facilitating the reliable and efficient reaction dynamics simulations that can reproduce well the experimental outcomes and examine associated atomic-molecular level mechanisms. Moreover, we found surprisingly high “intrinsic” reactivity of S(N)2 when the E2 pathway is completely blocked, indicating the reaction that intends to proceed via E2 transits to S(N)2 instead, due to a shared pre-reaction minimum. This finding indicates that the competing factor of E2 but not the steric hindrance determines the small reactivity of S(N)2 for the F(−) + (CH(3))(3)CI reaction. Our study provides new insight into the dynamical origin that determines the intrinsic reactivity in gas-phase organic chemistry. Nature Publishing Group UK 2022-07-30 /pmc/articles/PMC9338938/ /pubmed/35907925 http://dx.doi.org/10.1038/s41467-022-32191-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lu, Xiaoxiao
Shang, Chenyao
Li, Lulu
Chen, Rongjun
Fu, Bina
Xu, Xin
Zhang, Dong H.
Unexpected steric hindrance failure in the gas phase F(−) + (CH(3))(3)CI S(N)2 reaction
title Unexpected steric hindrance failure in the gas phase F(−) + (CH(3))(3)CI S(N)2 reaction
title_full Unexpected steric hindrance failure in the gas phase F(−) + (CH(3))(3)CI S(N)2 reaction
title_fullStr Unexpected steric hindrance failure in the gas phase F(−) + (CH(3))(3)CI S(N)2 reaction
title_full_unstemmed Unexpected steric hindrance failure in the gas phase F(−) + (CH(3))(3)CI S(N)2 reaction
title_short Unexpected steric hindrance failure in the gas phase F(−) + (CH(3))(3)CI S(N)2 reaction
title_sort unexpected steric hindrance failure in the gas phase f(−) + (ch(3))(3)ci s(n)2 reaction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338938/
https://www.ncbi.nlm.nih.gov/pubmed/35907925
http://dx.doi.org/10.1038/s41467-022-32191-6
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